OPIATE PEPTIDES AND RECEPTORS IN THE FAT/FAT MICE

候选人Yemiliya Berman博士拥有哈佛大学的博士学位 分子生物学研究所，莫斯科，俄罗斯。她是一个研究人员 纽约大学药理学系助理教授 大学医学中心。长期的职业目标将是获得 对阿片肽及其参与调控的认识 生理功能。纽约大学医学中心和R.L. Devi的实验室提供了必要的智力环境 制定一套强有力的研究计划。此外，L.Devi博士 将建议和指导候选人成为一名独立科学家， 致力于富有成效的生物医学研究事业。 候选人的职业目标是调查阿片类药物的作用 系统在肥胖/肥胖的小鼠模型中。这个小鼠模型是 缺乏参与成熟的一种酶--羧肽酶E 阿片肽和一个受调节的分泌途径分类受体。 在肥胖/肥胖小鼠的大脑中，完全 加工的阿片肽和COOH-水平的大幅增加- 末端延伸肽，含高相对分子质量强啡肽 多肽和未加工的前强啡肽。在这项拨款申请中， IR-强啡肽和IR-脑啡肽的区域分布 肥胖/肥胖小鼠成年和发育中大脑的mRNA水平将是 审查(具体目标1)。这些研究将提供关于 水平的差异分布和发育变化 阿片肽。强啡肽水平变化的影响 阿片受体系统上的多肽将在成人和 培育肥胖/肥胖小鼠(特定目标2)。受体总数和 激动剂刺激的GTP[g-35S]结合将通过 放射自显影和腺苷环化酶活性将用于 微米阿片受体、β阿片受体和kappa阿片受体的功能量化。 这些研究将有助于理解阿片受体系统是如何 适应不完全多肽加工。损害的假说 肥胖/肥胖小鼠对前强啡肽的处理是不正确的结果 将对不受监管的分类和分泌进行评估 (具体目标3)。这些研究将提供关于CPE如何 阻断导致前强啡肽加工和释放不完整 异常现象。脂肪/脂肪和瘦肉仔鼠的反应性 对微米级、Delta和Kappa激动剂和拮抗剂 将检查喂食行为(具体目标4)。激动剂或 拮抗剂将被急性给药和累积食物摄入量 注射后一小时将确定。剂量反应 将生成曲线。这些研究将提供关于 阿片受体类型参与肥胖/肥胖小鼠的喂养和 肥胖的发展。

The candidate, Dr. Yemiliya Berman, holds a Ph.D. degree from the Institute of Molecular Biology, Moscow, Russia. She is a Research Assistant Professor in the Department of Pharmacology at the New York University Medical Center. The long-term career goals will be to gain an understanding of opioid peptides and their involvement in modulating physiological functions. New York University Medical Center and R. L. Devi's laboratory provides the intellectual environment necessary for the development of a strong research program. In addition, Dr. L. Devi will advise and guide the candidate to become an independent scientist, committed to a productive biomedical research career. The candidate's career goal is to investigate the role of the opioid system in a mouse model for obesity fat/fat. This mouse model is deficient in carboxypeptidase E, an enzyme involved in the maturation of opioid peptides and a regulated secretory pathway sorting receptor. In the brain of fat/fat mice there is a large decrease in fully processed opioid peptides and a large increase in the level of COOH- terminal extended peptides, high molecular weight dynorphin containing peptides and unprocessed prodynorphin. In this grant application the regional distribution of ir-dynorphin and ir-enkephalin peptides and mRNA levels in adult and developing brains of fat/fat mice will be examined (specific aim 1). These studies will provide information on the differential distribution and developmental variations in the levels of opioid peptides. The effect of changes in the levels of dynorphin peptides on the opiate receptor system will be examined in adult and developing fat/fat mice (specific aim 2). Total receptor number and agonist stimulated GTP [g-35S] binding will be measured by autoradiography and adenylyl cyclase activity will be used for functional quantification of microns, delta and kappa opioid receptors. These studies will help to understand how the opiate receptor system adapt to incomplete peptide processing. The hypothesis that impaired Prodynorphin processing in the fat/fat mice is a result of incorrect sorting and secretion in an unregulated manner will be evaluated (specific aim 3). These studies will provide information on how CPE obliteration leads to incomplete Prodynorphin processing and release abnormalities. The responsiveness of fat/fat and lean littermate mice to microns, delta and kappa agonists and antagonists in terms of their feeding behavior will be examined (specific aim 4). Agonists or antagonists will be administered acutely and cumulative food intake in the one hour following injection will be determined. Dose response curves will be generated. These studies will provide information on opioid receptor types involved in feeding of fat/fat mice and development of obesity.